High‐fat and high‐sodium diet induces metabolic dysfunction in the absence of obesity

Abstract Objective Excess dietary fat and sodium (NaCl) are both associated with obesity and metabolic dysfunction. In mice, high NaCl has been shown to block high‐fat (HF) diet–induced weight gain. Here, the impact of an HF/NaCl diet on metabolic function in the absence of obesity was investigated. Methods Wild‐type mice were administered chow, NaCl (4%), HF, and HF/NaCl diets. Metabolic analysis was performed by measuring fasted blood glucose and insulin levels and by glucose tolerance test and insulin tolerance test. Results After 10 weeks on diets, male and female mice on the HF diet gained weight, and HF/NaCl mice had significantly reduced weight gain similar to chow‐fed mice. In the absence of obesity, HF/NaCl mice had significantly elevated fasting blood glucose and impaired glucose control during glucose tolerance tests. Both NaCl and HF/NaCl mice had decreased pancreas and β‐cell mass. Administration of NaCl in drinking water did not protect mice from HF‐diet‐induced weight gain and obesity. Further analysis revealed that longer administration of HF/NaCl diets for 20 weeks resulted in significant weight gain and insulin resistance. Conclusions The data demonstrate that despite early inhibitory effects on fat deposition and weight gain, an HF/NaCl diet does not prevent the metabolic consequences of HF diet consumption.